Jeffrey Malatack - Academia.edu (original) (raw)

Papers by Jeffrey Malatack

Journal of Pediatric Surgery, 2008

In children, therapeutic management of immunosuppression relies on allograft function, drug level... more In children, therapeutic management of immunosuppression relies on allograft function, drug levels, and clinical insight. Using a Food and Drug Administration-approved test for T-cell response, T-cell activation in vitro can be measured to monitor the immune response. Methods: In a retrospective study, 92 posttransplant children who received either a liver and/or kidney transplant and were followed by routine screening had their T-cell response tested by the Cylex ImmuKnow assay (Columbia, MD). After phytohemagglutinin-L stimulation of T-cells, adenosine triphosphate (ATP) concentrations were measured. In this assay, light emission at λ = 562 nm is proportional to the ATP concentration (ng/mL). Immunosuppressive drug trough levels were also measured. Quantitative real-time polymerase chain reaction Epstein-Barr virus (EBV) viral titers were determined for 2 patients. Results: Separating the results into younger than 12 years and 12-year or older populations, we found that for the younger than 12 years, 28% of patients were in the low immune function category, 47% in the moderate, and 25% in the high category. For the 12 years or older, 25% of patients were in the low immune function category, 47% in the moderate, and 28% in the high category. The immune function distribution was not different (P = not significant) between the younger than 12 years and 12-year or older groups. Tacrolimus trough levels were 6.3 ± 2.4 ng/mL for younger than 12 years and 5.6 ± 3.3 ng/mL for 12 years or older (P = not significant), and rapamycin was similar, but both showed no correlation to immune function. We observed increased ATP values with decreased EBV viral loads. Conclusions: These results suggest that tacrolimus and/or rapamycin levels do not adequately determine the biologic effect of immunosuppression. We expect that future T-cell activation monitoring will allow us to diminish rejection and infection events posttransplantation and lead to a healthier pediatric transplant population.

Genetics in Medicine, Sep 1, 2019

To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocu... more To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. Methods: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members. Results: We found the heterozygous missense variant in the ɑkinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis. Conclusion: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.

PubMed, Dec 1, 1983

The purgatory in which liver transplantation was mired has ended in the cyclosporine era. Long-te... more The purgatory in which liver transplantation was mired has ended in the cyclosporine era. Long-term survival after liver replacement was achieved in 1964 with dogs 1 and in humans 2 beginning in 1967. The longest surviving patient is now in her 14th postoperative year. In spite of such tantalizing successes, the operation was unpredictable and unreliable, with 1-year survival rates that did not improve with increased experience over a 16-year period. 3 Of the first 111 patients, less than 1/3 lived for 1 year. The 1-year survival rose to 50% in a second but small series of 30 patients, but in a third series, the survival sank again, almost to the original level. The overall 1-year survival rate for 170 patients was 33%.

Transplantation Proceedings, Dec 1, 1983

plantation was mired has ended in the cyclosporine era. Long-term survival after liver replacemen... more plantation was mired has ended in the cyclosporine era. Long-term survival after liver replacement was achieved in 1964 with dogs I and in humans 2 beginning in 1967. The longest surviving patient is now in her 14th postoperative year. In spite of such tantalizing successes, the operation was unpredictable and unreliable, with I-year survival rates that did not improve with increased experience over a 16year period. 3 Of the first III patients, less than 1/3 lived for 1 year. The I-year survival rose to 50% in a second but small series of 30 patients, but in a third series, the survival sank again, almost to the original level. The overall I-year survival rate for 170 patients was 33%.

Pediatric Transplantation, 2011

PubMed, Feb 1, 1985

1172 WBC count, BUN and serum creatinine, direct and total bilirubin, alanine aminotransferase (A... more 1172 WBC count, BUN and serum creatinine, direct and total bilirubin, alanine aminotransferase (AL T), aspartate aminotransferase (AST), alkaline phosphatase, and gamma glutamyl transferase (GGT).

The Journal of Pediatrics, May 1, 1982

The new immunosuppressive agent, cyclosporin A, was used with low doses of steroids to treat eigh... more The new immunosuppressive agent, cyclosporin A, was used with low doses of steroids to treat eight patients undergoing hepatic transplantation and three patients undergoing cadaveric renal transplantation. Seven of the eight liver recipients are well, including one who was given two livers. The three kidney recipients, who had developed cytotoxic antibodies after previously rejecting grafts with conventional immunosuppressive therapy, have had good results despite conditions which usually preclude attempts at transplantation. The ability to control rejection effectively and safely without chronic high-dose steroid therapy may make the described therapeutic regimen valuable for pediatric recipients of whole organs. Cadaveric organ transplantation in infants and children has been an unreliable and morbidity-laden undertaking. The ability to control rejection has been unpredictable with conventional immunosuppressive therapy including azathioprine and prednisone with or without anti-lymphocyte globulin. Even with "success" the frequent need for high-dose steroid therapy has all too often degraded the quality of post-transplantation life. We report here an alternative method of immunosuppression with cyclosporin A and low doses of steroids that has been used in eight liver and three cadaveric kidney recipients who have been followed for 3½ months to 1⅓ years. Although the experience is small and the follow-up periods short, the results have made us believe that transplantation of a variety of organs will become a practical reality in larger numbers of pediatric health care centers. METHODS Case material Liver recipients-The eight patients were 2⅙ to 16 years of age (Table I). Four had biliary atresia; of these, three had had one or more previous attempts at porticoenterostomy (Kasai procedure), and the earlier operations made transplantation difficult. Other diagnoses are shown in Table I.

Radiology, Nov 1, 1985

Over 45 months, 119 angiographic examinations were performed in 95 patients prior to liver transp... more Over 45 months, 119 angiographic examinations were performed in 95 patients prior to liver transplantation, and 53 examinations in 44 patients after transplantation. Transplantation feasibility was influenced by patency of the portal vein and inferior vena cava. Selective arterial portography, wedged hepatic venography, and transhepatic portography were used to assess the portal vein if sonography or computed tomography was inconclusive. Major indications for angiography after transplantation included early liver failure, sepsis, unexplained elevation of liver enzyme levels, and delayed bile leakage, all of which may be due to hepatic artery thrombosis. Other indications included gastrointestinal tract bleeding, hemobilia, and evaluation of portal vein patency in patients with chronic rejection who were being considered for retransplantation. Normal radiographic features of hepatic artery and portal vein reconstruction are demonstrated. Complications diagnosed using results of angiography included hepatic artery or portal vein stenoses and thromboses and pancreaticoduodenal aneurysms. Intrahepatic arterial narrowing, attenuation, slow flow, and poor filling were seen in five patients with rejection Index terms Liver; angiography; 952.122; 957.124; Liver; transplantation; 761.45 The first human liver transplantation was performed in 1963 (1). By 1966, six patients had received liver transplants at the University of Colorado Medical Center. Unfortunately, all of them soon died, with the longest survival being 23 days (2). The first extended survival (13 months) was achieved in 1967 (3). As survival rates have improved, transplantation has increasingly become an accepted mode of therapy for irreversible end-stage liver disease in both children and adults (4,5). The number of transplantations performed each year has steadily increased (2,4,5).

The Lancet, Jun 1, 1984

A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hyperchol... more A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hypercholesterolaemia underwent orthotopic cardiac transplantation and her liver was replaced with the liver of the same donor. In the first 10 weeks after transplantation serum cholesterol fell to 270 mg/dl from preoperative concentrations of more than 1000 mg/dl.

PubMed, Dec 1, 1983

C YCLOSPORINE (CsA) used with steroids has been a major influence in the improved survival of pat... more C YCLOSPORINE (CsA) used with steroids has been a major influence in the improved survival of patients undergoing orthotopic liver transplantation. The overall results of patient survival have been published elsewhere. I • 2 Part of the increased survival rate is dependent on retransplantation for homograft failure. We report our experience of patient and homograft survival as well as major causes for graft failure. MATERIALS AND METHODS From May II. 1981. to March 7. 1983.43 patients ranging in age from 7'/2 months to 18 years received 57 orthotopic liver homografts. Table I lists the indications for transplantation. Patients reported here have been assigned OT (orthotopic transplant) numbers. which allows one to follow and compare the course of anyone patient in previous or subsequent publications. Details of patient selection and immunosuppression have been described in detail e1sewhere.'-J Briefly. patients were given oral CsA (17.5 mgjkg) or an intravenous infusion of CsA (5 mgjkg) a few hours preoperatively. Intravenous CsA was continued at 5 mg/kgjday. divided twice daily. until oral CsA could be begun at 17.5 mg/kgjday. divided twice daily. Most pediatric patients were given a burst of steroids beginning the day of surgery (100 mg methylprednisolone) and rapidly tapered to a baseline dose (20 mgjday of prednisone) 4-5 days postoperatively. This baseline steroid dose was further decreased pending the patient's clinical course. If clinical signs of rejection appeared. the immunosuppression regimen was modified. Initially. a single bolus of hydrocortisone (500-1000 mg) was given intravenously. If the patient showed only moderate improvement, a cycle of prednisone similar to that given immediately postoperatively was also begun. In addition. CsA doses were occasionally increased. monitoring clinical and laboratory evidence for nephrotoxicity. Whole blood CsA levels were

Archives of pediatrics & adolescent medicine, Jun 1, 1989

An isolated marked transient rise in serum alkaline phosphatase levels in otherwise healthy child... more An isolated marked transient rise in serum alkaline phosphatase levels in otherwise healthy children is a well-documented occurrence. However, in children undergoing liver transplantation, elevated alkaline phosphatase values raise the possibility of biliary obstruction, rejection, or both. During a 6-year period, 6 of 278 children undergoing liver transplantation exhibited a similar phenomenon as an isolated abnormality. None had rejection, biliary obstruction, or other allograft dysfunction during a long follow-up. Eventually and without intervention, the alkaline phosphatase levels returned to normal. These instructive cases suggest that caution be used in advocating Invasive procedures if elevated alkaline phosphatase levels are an isolated abnormality, and close observation with noninvasive testing is recommended. After orthotopic liver transplantation, liver function test results are serially determined to monitor allograft function. Serum alkaline phosphatase (AP) and γ-glutamyltransferase (GGT) levels, when markedly elevated, lead to a strong suspicion of either allograft rejection or biliary obstruction. Further investigations, sometimes invasive, are often required to elucidate the exact problem. An isolated, transient, marked elevation of serum AP levels without any evidence of biliary obstruction has been reported in infants and children who have not undergone transplantation. 1-7 Infusions of serum albumin 8 and therapy with sulfamethoxazole-trimethoprim 9 have been reported to cause elevation of AP levels, but the cause in most patients is unknown. We have encountered six children who had an isolated, transient, marked elevation of serum AP levels at varying intervals following liver transplantation without evidence of biliary obstruction or rejection. The intent of this article is to bring this problem to the attention of physicians caring for pediatric liver transplant recipients and to urge caution in advocating invasive procedures. Patients and Methods During the years 1981 through 1986, 278 children received 378 liver transplants in the University of Pittsburgh (Pa) Children's Hospital transplant program. Part of the postoperative follow-up after discharge consisted of periodic checks of body weight, a complete blood cell count, and determinations of prothrombin and partial thromboplastin times, serum total bilirubin, alanine and aspartate aminotransferases, AP, GGT, calcium, and

The Lancet, 1985

Oral thrush developed during the second month of life in the 5-month-old son of a patient with ha... more Oral thrush developed during the second month of life in the 5-month-old son of a patient with haemophilia A. He did not feed well, and interstitial pneumonitis, lymphadenopathy, hepatosplenomegaly, and a cellular immune defect consistent with the acquired immunodeficiency syndrome (AIDS) followed. Both parents had signs of pre-AIDS during the year before their son's illness. Transmission presumably occurred in 3 steps: parenterally, via factor VIII concentrate in the haemophiliac; heterosexually, from the haemophiliac to his wife; and vertically, from mother to infant, or via close paternal-infant or maternal-infant contact. This first report of AIDS in the child of a haemophiliac supports the theory that AIDS is caused by an infectious agent. Concentrate-treated haemophiliacs may transmit this agent to their spouses or children, resulting in pre-AIDS or AIDS.

Biology of Blood and Marrow Transplantation, 2010

Pediatrics, Jul 1, 1984

During a 24-month period (May 1981 to May 1983), 47 pediatric patients (ranging in age from 7 mon... more During a 24-month period (May 1981 to May 1983), 47 pediatric patients (ranging in age from 7 months to 18 years) underwent orthotopic liver transplantation using cyclosporine and prednisone. Major indications were biliary atresia/hypoplasia, and metabolic liver disease. Thirty-two of 138 patients evaluated for the procedure died prior to transplantation. Thirty patients are alive from 6 to 29 months later including 7/15 patients who required retransplantation. Twenty-one of 32 patients are alive at 1 year following initial transplantation. All 30 survivors are clinically well and living at home; only one has an-abnormal bilirubin-level. Serious, lifethreatening medical and surgical complications were i:ommon during' the early months following transplantation. With one exception, deaths and major rejection

Annals of Internal Medicine, 1994

Journal of Pediatric Surgery, 1989

A 17-yr-old female received a liver transplant for type I glycogen storage disease. A year later,... more A 17-yr-old female received a liver transplant for type I glycogen storage disease. A year later, when she experienced variceal gastrointestinal hemorrhage, an angiogram revealed thrombosis of the portal vein with hepatopetal collateral channels. A distal splenorenal shunt was performed because of failure of sclerotherapy to control subsequent bleeding episodes and the fact that the liver function was normal. This patient continues to have normal hepatic function with a patent splenorenal shunt 4 yr after the shunting procedure. This case illustrates the feasibility of a distal splenorenal shunt to alleviate portal hypertension in cases of thrombosis of the portal vein following hepatic transplantation if the liver function is normal.

Journal of Pediatric Surgery, 2008

In children, therapeutic management of immunosuppression relies on allograft function, drug level... more In children, therapeutic management of immunosuppression relies on allograft function, drug levels, and clinical insight. Using a Food and Drug Administration-approved test for T-cell response, T-cell activation in vitro can be measured to monitor the immune response. Methods: In a retrospective study, 92 posttransplant children who received either a liver and/or kidney transplant and were followed by routine screening had their T-cell response tested by the Cylex ImmuKnow assay (Columbia, MD). After phytohemagglutinin-L stimulation of T-cells, adenosine triphosphate (ATP) concentrations were measured. In this assay, light emission at λ = 562 nm is proportional to the ATP concentration (ng/mL). Immunosuppressive drug trough levels were also measured. Quantitative real-time polymerase chain reaction Epstein-Barr virus (EBV) viral titers were determined for 2 patients. Results: Separating the results into younger than 12 years and 12-year or older populations, we found that for the younger than 12 years, 28% of patients were in the low immune function category, 47% in the moderate, and 25% in the high category. For the 12 years or older, 25% of patients were in the low immune function category, 47% in the moderate, and 28% in the high category. The immune function distribution was not different (P = not significant) between the younger than 12 years and 12-year or older groups. Tacrolimus trough levels were 6.3 ± 2.4 ng/mL for younger than 12 years and 5.6 ± 3.3 ng/mL for 12 years or older (P = not significant), and rapamycin was similar, but both showed no correlation to immune function. We observed increased ATP values with decreased EBV viral loads. Conclusions: These results suggest that tacrolimus and/or rapamycin levels do not adequately determine the biologic effect of immunosuppression. We expect that future T-cell activation monitoring will allow us to diminish rejection and infection events posttransplantation and lead to a healthier pediatric transplant population.

Genetics in Medicine, Sep 1, 2019

To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocu... more To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. Methods: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members. Results: We found the heterozygous missense variant in the ɑkinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis. Conclusion: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.

PubMed, Dec 1, 1983

The purgatory in which liver transplantation was mired has ended in the cyclosporine era. Long-te... more The purgatory in which liver transplantation was mired has ended in the cyclosporine era. Long-term survival after liver replacement was achieved in 1964 with dogs 1 and in humans 2 beginning in 1967. The longest surviving patient is now in her 14th postoperative year. In spite of such tantalizing successes, the operation was unpredictable and unreliable, with 1-year survival rates that did not improve with increased experience over a 16-year period. 3 Of the first 111 patients, less than 1/3 lived for 1 year. The 1-year survival rose to 50% in a second but small series of 30 patients, but in a third series, the survival sank again, almost to the original level. The overall 1-year survival rate for 170 patients was 33%.

Transplantation Proceedings, Dec 1, 1983

plantation was mired has ended in the cyclosporine era. Long-term survival after liver replacemen... more plantation was mired has ended in the cyclosporine era. Long-term survival after liver replacement was achieved in 1964 with dogs I and in humans 2 beginning in 1967. The longest surviving patient is now in her 14th postoperative year. In spite of such tantalizing successes, the operation was unpredictable and unreliable, with I-year survival rates that did not improve with increased experience over a 16year period. 3 Of the first III patients, less than 1/3 lived for 1 year. The I-year survival rose to 50% in a second but small series of 30 patients, but in a third series, the survival sank again, almost to the original level. The overall I-year survival rate for 170 patients was 33%.

Pediatric Transplantation, 2011

PubMed, Feb 1, 1985

1172 WBC count, BUN and serum creatinine, direct and total bilirubin, alanine aminotransferase (A... more 1172 WBC count, BUN and serum creatinine, direct and total bilirubin, alanine aminotransferase (AL T), aspartate aminotransferase (AST), alkaline phosphatase, and gamma glutamyl transferase (GGT).

The Journal of Pediatrics, May 1, 1982

The new immunosuppressive agent, cyclosporin A, was used with low doses of steroids to treat eigh... more The new immunosuppressive agent, cyclosporin A, was used with low doses of steroids to treat eight patients undergoing hepatic transplantation and three patients undergoing cadaveric renal transplantation. Seven of the eight liver recipients are well, including one who was given two livers. The three kidney recipients, who had developed cytotoxic antibodies after previously rejecting grafts with conventional immunosuppressive therapy, have had good results despite conditions which usually preclude attempts at transplantation. The ability to control rejection effectively and safely without chronic high-dose steroid therapy may make the described therapeutic regimen valuable for pediatric recipients of whole organs. Cadaveric organ transplantation in infants and children has been an unreliable and morbidity-laden undertaking. The ability to control rejection has been unpredictable with conventional immunosuppressive therapy including azathioprine and prednisone with or without anti-lymphocyte globulin. Even with "success" the frequent need for high-dose steroid therapy has all too often degraded the quality of post-transplantation life. We report here an alternative method of immunosuppression with cyclosporin A and low doses of steroids that has been used in eight liver and three cadaveric kidney recipients who have been followed for 3½ months to 1⅓ years. Although the experience is small and the follow-up periods short, the results have made us believe that transplantation of a variety of organs will become a practical reality in larger numbers of pediatric health care centers. METHODS Case material Liver recipients-The eight patients were 2⅙ to 16 years of age (Table I). Four had biliary atresia; of these, three had had one or more previous attempts at porticoenterostomy (Kasai procedure), and the earlier operations made transplantation difficult. Other diagnoses are shown in Table I.

Radiology, Nov 1, 1985

Over 45 months, 119 angiographic examinations were performed in 95 patients prior to liver transp... more Over 45 months, 119 angiographic examinations were performed in 95 patients prior to liver transplantation, and 53 examinations in 44 patients after transplantation. Transplantation feasibility was influenced by patency of the portal vein and inferior vena cava. Selective arterial portography, wedged hepatic venography, and transhepatic portography were used to assess the portal vein if sonography or computed tomography was inconclusive. Major indications for angiography after transplantation included early liver failure, sepsis, unexplained elevation of liver enzyme levels, and delayed bile leakage, all of which may be due to hepatic artery thrombosis. Other indications included gastrointestinal tract bleeding, hemobilia, and evaluation of portal vein patency in patients with chronic rejection who were being considered for retransplantation. Normal radiographic features of hepatic artery and portal vein reconstruction are demonstrated. Complications diagnosed using results of angiography included hepatic artery or portal vein stenoses and thromboses and pancreaticoduodenal aneurysms. Intrahepatic arterial narrowing, attenuation, slow flow, and poor filling were seen in five patients with rejection Index terms Liver; angiography; 952.122; 957.124; Liver; transplantation; 761.45 The first human liver transplantation was performed in 1963 (1). By 1966, six patients had received liver transplants at the University of Colorado Medical Center. Unfortunately, all of them soon died, with the longest survival being 23 days (2). The first extended survival (13 months) was achieved in 1967 (3). As survival rates have improved, transplantation has increasingly become an accepted mode of therapy for irreversible end-stage liver disease in both children and adults (4,5). The number of transplantations performed each year has steadily increased (2,4,5).

The Lancet, Jun 1, 1984

A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hyperchol... more A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hypercholesterolaemia underwent orthotopic cardiac transplantation and her liver was replaced with the liver of the same donor. In the first 10 weeks after transplantation serum cholesterol fell to 270 mg/dl from preoperative concentrations of more than 1000 mg/dl.

PubMed, Dec 1, 1983

C YCLOSPORINE (CsA) used with steroids has been a major influence in the improved survival of pat... more C YCLOSPORINE (CsA) used with steroids has been a major influence in the improved survival of patients undergoing orthotopic liver transplantation. The overall results of patient survival have been published elsewhere. I • 2 Part of the increased survival rate is dependent on retransplantation for homograft failure. We report our experience of patient and homograft survival as well as major causes for graft failure. MATERIALS AND METHODS From May II. 1981. to March 7. 1983.43 patients ranging in age from 7'/2 months to 18 years received 57 orthotopic liver homografts. Table I lists the indications for transplantation. Patients reported here have been assigned OT (orthotopic transplant) numbers. which allows one to follow and compare the course of anyone patient in previous or subsequent publications. Details of patient selection and immunosuppression have been described in detail e1sewhere.'-J Briefly. patients were given oral CsA (17.5 mgjkg) or an intravenous infusion of CsA (5 mgjkg) a few hours preoperatively. Intravenous CsA was continued at 5 mg/kgjday. divided twice daily. until oral CsA could be begun at 17.5 mg/kgjday. divided twice daily. Most pediatric patients were given a burst of steroids beginning the day of surgery (100 mg methylprednisolone) and rapidly tapered to a baseline dose (20 mgjday of prednisone) 4-5 days postoperatively. This baseline steroid dose was further decreased pending the patient's clinical course. If clinical signs of rejection appeared. the immunosuppression regimen was modified. Initially. a single bolus of hydrocortisone (500-1000 mg) was given intravenously. If the patient showed only moderate improvement, a cycle of prednisone similar to that given immediately postoperatively was also begun. In addition. CsA doses were occasionally increased. monitoring clinical and laboratory evidence for nephrotoxicity. Whole blood CsA levels were

Archives of pediatrics & adolescent medicine, Jun 1, 1989

An isolated marked transient rise in serum alkaline phosphatase levels in otherwise healthy child... more An isolated marked transient rise in serum alkaline phosphatase levels in otherwise healthy children is a well-documented occurrence. However, in children undergoing liver transplantation, elevated alkaline phosphatase values raise the possibility of biliary obstruction, rejection, or both. During a 6-year period, 6 of 278 children undergoing liver transplantation exhibited a similar phenomenon as an isolated abnormality. None had rejection, biliary obstruction, or other allograft dysfunction during a long follow-up. Eventually and without intervention, the alkaline phosphatase levels returned to normal. These instructive cases suggest that caution be used in advocating Invasive procedures if elevated alkaline phosphatase levels are an isolated abnormality, and close observation with noninvasive testing is recommended. After orthotopic liver transplantation, liver function test results are serially determined to monitor allograft function. Serum alkaline phosphatase (AP) and γ-glutamyltransferase (GGT) levels, when markedly elevated, lead to a strong suspicion of either allograft rejection or biliary obstruction. Further investigations, sometimes invasive, are often required to elucidate the exact problem. An isolated, transient, marked elevation of serum AP levels without any evidence of biliary obstruction has been reported in infants and children who have not undergone transplantation. 1-7 Infusions of serum albumin 8 and therapy with sulfamethoxazole-trimethoprim 9 have been reported to cause elevation of AP levels, but the cause in most patients is unknown. We have encountered six children who had an isolated, transient, marked elevation of serum AP levels at varying intervals following liver transplantation without evidence of biliary obstruction or rejection. The intent of this article is to bring this problem to the attention of physicians caring for pediatric liver transplant recipients and to urge caution in advocating invasive procedures. Patients and Methods During the years 1981 through 1986, 278 children received 378 liver transplants in the University of Pittsburgh (Pa) Children's Hospital transplant program. Part of the postoperative follow-up after discharge consisted of periodic checks of body weight, a complete blood cell count, and determinations of prothrombin and partial thromboplastin times, serum total bilirubin, alanine and aspartate aminotransferases, AP, GGT, calcium, and

The Lancet, 1985

Oral thrush developed during the second month of life in the 5-month-old son of a patient with ha... more Oral thrush developed during the second month of life in the 5-month-old son of a patient with haemophilia A. He did not feed well, and interstitial pneumonitis, lymphadenopathy, hepatosplenomegaly, and a cellular immune defect consistent with the acquired immunodeficiency syndrome (AIDS) followed. Both parents had signs of pre-AIDS during the year before their son's illness. Transmission presumably occurred in 3 steps: parenterally, via factor VIII concentrate in the haemophiliac; heterosexually, from the haemophiliac to his wife; and vertically, from mother to infant, or via close paternal-infant or maternal-infant contact. This first report of AIDS in the child of a haemophiliac supports the theory that AIDS is caused by an infectious agent. Concentrate-treated haemophiliacs may transmit this agent to their spouses or children, resulting in pre-AIDS or AIDS.

Biology of Blood and Marrow Transplantation, 2010

Pediatrics, Jul 1, 1984

During a 24-month period (May 1981 to May 1983), 47 pediatric patients (ranging in age from 7 mon... more During a 24-month period (May 1981 to May 1983), 47 pediatric patients (ranging in age from 7 months to 18 years) underwent orthotopic liver transplantation using cyclosporine and prednisone. Major indications were biliary atresia/hypoplasia, and metabolic liver disease. Thirty-two of 138 patients evaluated for the procedure died prior to transplantation. Thirty patients are alive from 6 to 29 months later including 7/15 patients who required retransplantation. Twenty-one of 32 patients are alive at 1 year following initial transplantation. All 30 survivors are clinically well and living at home; only one has an-abnormal bilirubin-level. Serious, lifethreatening medical and surgical complications were i:ommon during' the early months following transplantation. With one exception, deaths and major rejection

Annals of Internal Medicine, 1994

Journal of Pediatric Surgery, 1989

A 17-yr-old female received a liver transplant for type I glycogen storage disease. A year later,... more A 17-yr-old female received a liver transplant for type I glycogen storage disease. A year later, when she experienced variceal gastrointestinal hemorrhage, an angiogram revealed thrombosis of the portal vein with hepatopetal collateral channels. A distal splenorenal shunt was performed because of failure of sclerotherapy to control subsequent bleeding episodes and the fact that the liver function was normal. This patient continues to have normal hepatic function with a patent splenorenal shunt 4 yr after the shunting procedure. This case illustrates the feasibility of a distal splenorenal shunt to alleviate portal hypertension in cases of thrombosis of the portal vein following hepatic transplantation if the liver function is normal.